The United States and other developed countries are experiencing a severe shortage of professionals trained in biological and medical informatics. To retain a leading position at the forefront of modem biology, medicine, pharmaceutical sciences and agriculture, this shortage must be alleviated through the interdisciplinary training of predoctoral and postdoctoral fellows. The trainees must be educated in the development and application of mathematical and computational tools that will later enable them effectively to exploit the unprecedented opportunities, and tackle the novel challenges, brought forth by advances in genome technology and molecular biology. To this end, the Department of Biometry and Epidemiology at the Medical University of South Carolina requests funds for an educational program dedicated to the Training of Toolmakers in BioMedical Informatics (TTBMI). This program will educate graduate students and post-doctoral fellows in one focused niche of biomedical information for which MUSC is particularly well equipped. This niche comprises the development and application of methods of computational systems science for connecting genes with their biochemical, physiological and clinical functions. The Department has an established infrastructure and has offered curricula in biostatistics and biomedical systems science since the early 1970's. In 2000, the Department obtained approval from the State of South Carolina to offer a graduate program in biomedical informatics. The requested funds will be used to implement this effort. The proposed program consists of classroom teaching in informatics methods and relevant biological topics, which is subsequently enriched and complemented with hands-on, specific informatics research in one of the numerous participating programs that already exist on campus. Individuals from these programs have expressed enthusiastic support for the proposed program and, in particular, for a mechanism of co-mentoring trainees with faculty from the Department of Biometry and Epidemiology. Through the dual mechanism of informatics training and real- world application, graduates will be educated to become toolmakers capable of solving problems in biology and medicine of the 21st century.